S202: CHILDBEARING AMONG CLASSICAL HODGKIN LYMPHOMA SURVIVORS TREATED WITH BEACOPP AND ABVD IN SWEDEN, DENMARK, AND NORWAY
Authors: J. P. Entrop, C. E. Weibull, K. E. Smedby, L. H. Jakobsen, A. K. Øvlisen, D. Molin, I. Glimelius, A. Marklund, K. B. Smeland, T. C. El-Galaly, S. Eloranta
Journal: HemaSphere (2022)

Background: Recent studies have shown decreased childbearing rates in some classical Hodgkin lymphoma (cHL) survivors compared to the general population. This decrease is hypothesized to be caused by administered intensive chemotherapy. Understanding if currently used treatment protocols lead to reduced post-treatment childbirth potential is important as differential impact on childbearing may influence treatment decisions for younger patients. Firm conclusions from previous population-based studies have been hampered by low power for specific treatment contrasts. Aims: To increase understanding of differences in childbearing patterns among male and female HL survivors treated with ABVD and BEACOPP in a study combining population-based register data from Sweden, Denmark, and Norway. Methods: In this cohort study 2,937 individuals aged 18-40 years with a recorded diagnosis of cHL in the Swedish lymphoma register (SLR), the Danish lymphoma registry (LYFO), or the clinical database at Oslo University Hospital (OUH) between 1995 and 2019 were included. Information on first-line chemotherapy treatment was available in the registers. Treatment regimens were classified as ABVD, 6-8 BEACOPP, or other. The SLR, LYFO, and OUH databases were linked to national medical birth registers to obtain information on childbirths. Follow-up started 9 months after cHL diagnosis and was accrued until date of first childbirth, death, or administrative censoring (December 2017, 2018, or 2019 for Norway, Sweden, and Denmark, respectively) or after 10 years. Females were additionally censored at date of relapse or stem cell transplantation due to the limited accessibility of assisted reproductive techniques for female patients experiencing one of those events. Stratified Cox models allowing for effect modification between sex and treatment and adjusted for stage, age at diagnosis, year of diagnosis, parity, and performance status were used to estimate hazard ratios (HRs). Flexible parametric survival models were used to estimate marginal childbirth rates and standardized cumulative incidence of childbirth across treatment groups. A comprehensive study analysis plan been published and pre-registered on the Open Science Framework (https://osf.io/eumy5/). Results: In summary, 75% of HL patients were treated with ABVD and 10.8% with 6-8 BEACOPP. An additional 14.2% received other treatments or had missing treatment information and were excluded from further analyses. The rate of first childbirth per 1,000 person-years for males and females was 45.5 and 50.0 respectively in the ABVD group, and 23.8 and 43.5 in the 6-8 BEACOPP group. The adjusted HR of first childbirths for males and females, comparing patients treated with 6-8 BEACOPP to ABVD were 0.54 (95% CI 0.37-0.79) and 0.92 (95% CI 0.61-1.39) respectively. Plots of the cause-specific cumulative incidence functions (CIF) of childbirth show a constantly lower proportion of male patients with childbirths over time since HL diagnosis comparing patients treated with 6-8 BEACOPP and ABVD. However, this difference was not present among female patients. Adjusted marginal estimates of the cause-specific CIF of childbirth showed the same pattern. Image:Summary/Conclusion: BEACOPP treatment is associated with decreased childbearing rates in male but not female HL patients. Infertility counselling for this group is advisable.